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Synapses, those miniscule voids between neurons, or neurons and muscles, are an essential part of any nervous system-without them signals traveling along axons, the action potentials, will not propagate along their intended paths. But these tiny gaps are neither static nor permanent. Indeed the making and breaking of synapses is necessary for the development of a healthy nervous system and for the rewiring of fully developed systems. Without this "plasticity," for example, new tasks cannot be learned or new memories formed.

Plasticity can also be achieved without destroying or making new contacts. Some synapses exhibit a phenomenon called paired-pulse facilitation (PPF), whereby the synaptic response to a second action potential is much greater than the response to the first. For this to happen the second action potential must closely follow the first one, say within a few hundred milliseconds.

Paired-pulse facilitation is usually measured using groups of synapses. In this month's Nature Neuroscience, however, Karel Svoboda and colleagues at Cold Spring Harbor Laboratory, New York, report the measurement of PPF using single synapses. Their surprising results run contrary to the accepted rules for how synaptic active zones behave.

Synaptic active zones are discrete areas at the end of an axon that harbor vesicles filled with neurotransmitters and poised to dump it into the synapse. The "univesicular release rule" for synapses states that for a given action potential only one vesicle can be released per active zone. If this were the case, then paired-pulse facilitation could not increase the response size at a single active zone, as the second action potential would also only release one vesicle.

Oertner et al, studied the synapse between CA3 and CA1 pyramidal neurons of the hippocampus, as these glutametergic neurons contain only one active zone per synapse. The researchers used a two-photon laser scanning microscope that allowed them to track events at single synapses by measuring transient increases in calcium levels. Multiphoton microscopy is beginning to be used to study amyloid formation in Alzheimer's mouse models (see related news item, see related news item), raising the question whether it might also become a tool to investigate synaptic plasticity in these models. In the present study, Oertner et al. found that the potency of response to a second stimulus was greater than that to a stimulus given some milliseconds prior-thus demonstrating paired-pulse facilitation at a single synapse and debunking the univesicular release rule. Indeed, their data suggests that about 5 vesicles stand ready to be released per active zone, allowing for a much greater dynamic range of synaptic transmission.—Tom Fagan